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Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

Jacobsen ID, Grosse K, Berndt A, Hube B - PLoS ONE (2011)

Bottom Line: While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos.Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines.C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections.

View Article: PubMed Central - PubMed

Affiliation: Department for Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany. ilse.jacobsen@hki-jena.de

ABSTRACT
Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM) and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite its limitations, it presents a useful alternative tool to pre-screen C. albicans strains to select strains for subsequent testing in murine models.

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Addition of IL10 reduces mortality after C. albicans infection.On developmental day 10, embryos were treated with 100 ng recombinant chicken IL10 (IL10) in PBS/BSA or PBS/BSA alone ( ) and infected with 107 cfu C. albicans SC5314. Survival is shown as Kaplan-Meyer curve, n = 20 per group, two independent experiments. Treatment had a significant effect on survival (P<0.05, log rank test).
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pone-0019741-g004: Addition of IL10 reduces mortality after C. albicans infection.On developmental day 10, embryos were treated with 100 ng recombinant chicken IL10 (IL10) in PBS/BSA or PBS/BSA alone ( ) and infected with 107 cfu C. albicans SC5314. Survival is shown as Kaplan-Meyer curve, n = 20 per group, two independent experiments. Treatment had a significant effect on survival (P<0.05, log rank test).

Mentions: Age-dependent resistance of chicken embryos challenged with LPS or infected with C. albicans correlated with the transcription levels of IL-10 and IL-4. In mice, the role of IL-10 is not fully clear. While MacCallum et al. showed an inverse correlation of IL-10 with kidney lesion severity and suggested that IL-10 might exert a defensive role [11], Vazquez-Torres et al. demonstrated increased susceptibility of IL-10 knock out mice to systemic candidiasis [28]. To clarify the role of IL-10 in infected chicken embryos, we applied 100 ng recombinant chicken IL-10 onto the CAM of 10 days old eggs 15 min prior to infection. Controls were treated with carrier solution only. IL-10 application alone had no influence on survival of non-infected control embryos. In infected embryos, IL-10 treatment had a minor but reproducible and significant positive effect on survival (P<0.05) (Fig. 4).


Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

Jacobsen ID, Grosse K, Berndt A, Hube B - PLoS ONE (2011)

Addition of IL10 reduces mortality after C. albicans infection.On developmental day 10, embryos were treated with 100 ng recombinant chicken IL10 (IL10) in PBS/BSA or PBS/BSA alone ( ) and infected with 107 cfu C. albicans SC5314. Survival is shown as Kaplan-Meyer curve, n = 20 per group, two independent experiments. Treatment had a significant effect on survival (P<0.05, log rank test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094387&req=5

pone-0019741-g004: Addition of IL10 reduces mortality after C. albicans infection.On developmental day 10, embryos were treated with 100 ng recombinant chicken IL10 (IL10) in PBS/BSA or PBS/BSA alone ( ) and infected with 107 cfu C. albicans SC5314. Survival is shown as Kaplan-Meyer curve, n = 20 per group, two independent experiments. Treatment had a significant effect on survival (P<0.05, log rank test).
Mentions: Age-dependent resistance of chicken embryos challenged with LPS or infected with C. albicans correlated with the transcription levels of IL-10 and IL-4. In mice, the role of IL-10 is not fully clear. While MacCallum et al. showed an inverse correlation of IL-10 with kidney lesion severity and suggested that IL-10 might exert a defensive role [11], Vazquez-Torres et al. demonstrated increased susceptibility of IL-10 knock out mice to systemic candidiasis [28]. To clarify the role of IL-10 in infected chicken embryos, we applied 100 ng recombinant chicken IL-10 onto the CAM of 10 days old eggs 15 min prior to infection. Controls were treated with carrier solution only. IL-10 application alone had no influence on survival of non-infected control embryos. In infected embryos, IL-10 treatment had a minor but reproducible and significant positive effect on survival (P<0.05) (Fig. 4).

Bottom Line: While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos.Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines.C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections.

View Article: PubMed Central - PubMed

Affiliation: Department for Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany. ilse.jacobsen@hki-jena.de

ABSTRACT
Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM) and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite its limitations, it presents a useful alternative tool to pre-screen C. albicans strains to select strains for subsequent testing in murine models.

Show MeSH
Related in: MedlinePlus